The present invention relates to drug delivery and pertains particularly to a method and apparatus for the transtissue delivery of drugs and other molecules.
In my aforementioned application, I disclose an apparatus and method for the electroporation of drugs and genes into surface cells. In another co-pending application Ser. No. 07/907,322, entitled ELECTROPORATION METHOD AND APPARATUS FOR INSERTION OF DRUGS AND GENES INTO ENDOTHELIAL CELLS, filed Jul. 1, 1992, certain methods and apparatus are disclosed for insertion of drugs and genes into endothelial cells. It is often desirable to transport drugs and genes across or beyond a layer of surface tissue.
In the aforementioned parent application, I disclose methods and apparatus tier the electroporation of drugs and genes into surface cells. In that application, apparatus is disclosed for delivery of a fluid medium carrying preselected molecules to a skin surface and thereafter applying electrical signals by means of electrodes to the surface tissue. The field is applied at a predetermined strength and duration in order to make the walls of the cells of the skin transiently permeable to permit the macromolecules to enter the preselected cells without damaging them.
One difficulty with the prior apparatus is that the stratum corneum (SC) consists of a thin layer of dead cells with a high electrical resistance. This presents a major obstacle to the administration of drugs and genes transdermally. This layer can be perforated by the administration of short electrical field pulses, such as used in electroporation of cells. However, in the case of stratum corneum it appears more appropriate to speak in terms of dielectric break down of the stratum corneum.
Among the prior art relating generally to this field is the Weaver et al patent U.S. Pat. No. 5,019,034 entitled "Control of Transport of Molecules Across Tissue Using Electroporation". He describes a proposal for using high voltage, short duration electrical pulses on the tissue surface to produce electroporation of the tissue. However, he does not address or solve the problem of the obstacle provided by the stratum corneum, or how to drive the drugs into the tissue.
Another patent of interest is that of Grasso U.S. Pat. No. 4,955,378 entitled "Apparatus and Methods for Performing Electrofusion at Specific Anatomical Sites". He discloses a method of fusing biological particles to living tissue, preferably on corneas and in cervical areas. The tissue consists of living cells which are able to completely fuse with the biological particles, or live cells. Again, this does not address or solve the problem presented by the resistance of the stratum corneum. Also, neither of these patents provide or suggest any means to force the drugs or genes into or across the tissue surface.
The present invention was devised to overcome the problems of the prior art by providing means to overcome the resistance to the administration of drugs transdermally presented by the stratum corneum. It is also applicable to the transport of drugs and genes across surfaces of other tissue such as membranes.